Facilitating Implementation Science within the SIBS Genomics Study (SIBS-Gen-Gen) PROJECT SUMMARY Stroke, a leading cause of long-term disability, is still the second most common cause of death globally with its highest burden among people of African ancestry. Stroke is a complex trait with substantial genetic contribution. While MEGASTROKE identified certain genetic variants for ischemic stroke in other populations excluding indigenous Africans (IA), candidate gene studies within the Stroke Investigative Research and Education Network (SIREN) have reported some loci, and we are conducting the first genome-wide association study to unravel genetic determinants of stroke among indigenous Africans within the Systematic Investigation of Blacks with Stroke using Genomics (SIBS Genomics) study (R01- NS107900). While results of assessment of established risk factors such as hypertension is disclosed to stroke-free individuals, it is critical to validate its emerging genetic determinants before translation to practice community. Moreover, it is crucial to explore the implications of disclosure of the results of genetic test for stroke to stroke-free individuals and their family members. The ethical, clinical, and social implications of disclosure of genetic test results for clinically significant genetic determinants of polygenic traits such as stroke, has not been characterized among IA. To translate imminent and future findings from SIREN and SIBS Genomics studies into clinical and community services through implementation science, it is important to understand stroke-free individuals? perception, preferences and attitude towards disclosure of genetic results for stroke. Therefore, using the administrative supplement mechanism in response to NOT-TW-19-003, we will conduct an ancillary study to SIB-Genomics (R01-NS107900) called SIBS Genomics-Genetic counselling (SIBS-Gen-Gen) to prepare for generalization of its findings to practice and the population. We will investigate stroke-free individuals? perception, preferences and attitudes towards disclosure of results of genetic testing for stroke while building capacity for disclosure of results and genetic counselling for stroke. We will explore the various tiers of clinical utility of genetic variants using the diffusion of innovations theory to explore these at several levels of the socio-ecological model: a) individual: 427 stroke-free controls; b) their family/significant others; c) healthcare providers and d) community. We will also conduct a workshop on genetic counseling to train the research assistants, investigators, healthcare providers, and community engagement staff of SIBS Genomics on the disclosure of results of validated pathogenic genetic variants associated with stroke/polygenic risk score; and how to handle non-pathogenic results and variants of unknown significance. This study will provide pilot data for designing a randomized controlled trial on disclosure of stroke genetic tests results.